Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.

Recent studies strongly indicate that aberrations in the control of gene expression might contribute to the initiation and progression of Alzheimer’s disease (AD). In particular, alternative splicing has been suggested to play a role in spontaneous cases of AD.

This study provides, for the first time, transcriptomic analysis for distinct regions of the Alzheimer’s disease (AD) brain using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq analysis was used to survey transcriptome profiles from total brain, frontal and temporal lobe of healthy and AD post-mortem tissue. Gene expression levels, splicing isoforms and alternative transcript start sites were quantified.

Gene Ontology term enrichment analysis revealed an overrepresentation of genes associated with a neuron’s cytological structure and synapse function in AD brain samples. Analysis of the temporal lobe with the Cufflinks tool revealed that transcriptional isoforms of the apolipoprotein E gene, APOE-001, -002 and -005, are under the control of different promoters in normal and AD brain tissue. These results indicate that alternative splicing and promoter usage of the APOE gene in AD brain tissue might reflect the progression of neurodegeneration.

Twine NA, Janitz K, Wilkins MR, Janitz M. (2011) Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer’s disease. PLoS One 6(1), e16266. [article]